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Oleuropein attenuates 6-hydroxydopamine-induced cytotoxicity through redox regulation in differentiated dopaminergic neurons: potential involvement of RET-associated signalling

  • Bushra Y. Ahmed
    ,
  • Sigrun Lange
    ,
  • Mohamad Warda
    ,
  • Azizeh Shadidizaji
    ,
  • Pinar Uysal-Onganer
  • University of Westminster
    ,
  • Cairo University
    ,
  • Ataturk University
Research Output:
Contribution to journal
Article
 Peer-review

Open access

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by selective loss of dopamine-containing neurons (DCNs) in the substantia nigra. Oxidative stress and impaired neurotrophic signalling contribute to PD pathogenesis. Oleuropein (Ole), a phenolic compound found in olives and olive leaves, exhibits antioxidant and cytoprotective properties that may counteract neuronal injury. This study investigated the neuroprotective effects of Ole in differentiated dopaminergic neurons (dDCNs) derived from the human ReNcell VM model exposed to 6-hydroxydopamine (6-OHDA). Ole significantly attenuated 6-OHDA-induced cytotoxicity, restoring cell viability following post- and pre-treatment compared with toxin-treated cells. Tyrosine hydroxylase expression was preserved, indicating maintenance of the dopaminergic phenotype. Ole also reduced lipid peroxidation and restored total antioxidant capacity, supporting a role in redox homeostasis. Molecular docking suggested a stable interaction between Ole and the RET receptor tyrosine kinase, suggesting a potential involvement of RET-associated survival signalling pathways that requires further experimental validation. In addition, 6-OHDA altered extracellular vesicle (EV) release and EV-associated transcripts related to Wnt signalling (Wnt3a, Wnt5a, GSK3), while Ole partially restored EV release profiles and EV-associated Wnt signalling-related transcripts. Collectively, these findings indicate that Ole protects dDCNs from oxidative stress and highlight its potential as a neuroprotective agent against dopaminergic neuronal injury.

Publication Information

Output type

Research Output:
Contribution to journal
Article
 Peer-review

Original language

English

Article number

5892

Pages from-to (Number of pages)

Pages 5892

Journal (Volume, Issue Number)

International Journal of Molecular Sciences (Volume 27, Issue 13)

Publication milestones

  • Accepted/In press - 28/06/2026
  • Published - 30/06/2026

Publication status

Published - 30/06/2026

ISSN

1661-6596

Publication IDs

  • Scopus: 105044966085

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